This phase II trial is studying how well giving cetuximab together with bevacizumab works in treating patients with recurrent or metastatic head and neck cancer. Monoclonal antibodies, such as cetuximab and bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab and bevacizumab may also stop the growth of head and neck cancer by blocking blood flow to the tumor. Giving cetuximab together with bevacizumab may kill more tumor cells.

Objective response rate with the combination of cetuximab and bevacizumab in recurrent or metastatic head and neck cancer [ Time Frame: Baseline and every 3 weeks if using physical exam or plain x-ray or every 6 weeks if using CT scan or MRI ] [ Designated as safety issue: No ]

Evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The 95% confidence intervals should be provided.

Secondary Outcome Measures:

Overall survival of patients with recurrent or metastatic head and neck cancer treated with cetuximab plus bevacizumab [ Time Frame: Every 3 months for 2 years and then every 6 months for 3 years ] [ Designated as safety issue: No ]

Progression-free survival of patients with recurrent or metastatic head and neck cancer treated with cetuximab plus bevacizumab [ Time Frame: Every 2 months ] [ Designated as safety issue: No ]

Toxicity of cetuximab and bevacizumab in head and neck cancer patients. [ Time Frame: Evaluated on an ongoing basis ] [ Designated as safety issue: Yes ]

Graded using the Common terminology Criteria for Adverse Events (CTCAE) version 4.0.

Antitumor activity as measured by the level of biomarker in reverse phase protein arrays (RPPA) [ Time Frame: Baseline and day 21 of course 1 ] [ Designated as safety issue: No ]

The correlative study will evaluate the following biomarkers on tumor tissue using RPPA: EGFR, pEGFR, Src, pMAPK, pSTAT3, pSTAT5, pSTAT1, pAKT, p38, p21, p27, PARP, E-cadherin, p-ErbB3, Ki67, VEGF, and IL-8. In addition, we will examine EGFR gene copy number by FISH and serum EGFR. A 2-tailed Wilcoxon test at alpha = .01 will have 80% power to detect an increase or decrease of 0.9 for the "average" protein and 80% power to detect a difference of 1.8 in a protein with double the variability.

Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: bevacizumab

Given IV

Other Names:

anti-VEGF humanized monoclonal antibody

anti-VEGF monoclonal antibody

Avastin

rhuMAb VEGF

Biological: cetuximab

Given IV

Other Names:

C225

C225 monoclonal antibody

IMC-C225

MOAB C225

monoclonal antibody C225

Other: laboratory biomarker analysis

Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the objective response rate in patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with cetuximab and bevacizumab.

SECONDARY OBJECTIVES:

I. Determine the progression-free and overall survival of patients treated with this regimen.

III. Evaluate treatment-related toxicities of this regimen in these patients. IV. Collect and bank blood samples for future correlative studies.

OUTLINE: This is a multicenter study. Patients receive cetuximab intravenously (IV) over 1-2 hours on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples are collected at baseline to determine whether biomarkers on tumor tissue and/or blood can be linked with clinical response and to measure signaling pathways by reverse phase protein microarray. Epidermal growth factor receptor (EGFR) gene copy number is assessed by fluorescent in situ hybridization (FISH) on tumor tissue pretreatment. Blood samples are also collected at baseline and on day 21 of course 1 for analysis by acridinium-linked immunosorbent assay (ALISA) to quantify serum p110 sEGFR protein levels.

After completion of study treatment, patients are followed every 2-3 months for 2 years and then every 6 months for 3 years.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Histologically or cytologically confirmed squamous cell carcinoma of the head and neck

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00407810